This application requests funds to purchase an Applied Biosystems MDS SCIEX 4000 QTRAP triple quadrupole mass spectrometer and an Agilent 1200 LC system needed for operation of the LC/MS/MS instrument. The instrument will be used in a new lipid analysis core laboratory that will be established with the help of institutional funds and other commitments from Columbia University's Irving Institute for Clinical and Translational Research, which is the home of our NIH- funded Clinical Translational Science Award. The LC/MS/MS lipid analysis core laboratory will be used by thirteen NIH-funded investigators (the User Group members) from two units of Columbia University, the College of Physicians and Surgeons and the Lamont-Doherty Earth Observatory and by an investigator from the Department of Biology of the City College of New York. Lipids play fundamental roles in the prevention and development of chronic diseases. There is growing awareness that lipids, specifically many that are present at very low concentrations (in the nM range or lower), play critical roles in both maintaining normal health and in the development of chronic diseases, including cardiovascular disease, cancer, diabetes, liver disease, and neurological diseases. In order to unravel linkages between lipid metabolism and actions, and to determine how these lipids maintain a balance between chronic disease prevention and chronic disease development, the modern research laboratory focused on lipid physiology and pathophysiology must be able to assess routinely levels of low abundance, bioactive lipids. It is critical that assays be sensitive enough to determine how the qualitative and quantitative nature of these lipids differs between normal physiology and pathophysiology. The LC/MS/MS instrument we are proposing to purchase will be used primarily to undertake quantitative analyses of natural lipids and lipophilic substances that are present at very low levels in cells, tissues, biological fluids and other materials with the goal of gaining understanding of how these bioactive lipids contribute to the development and progression of chronic diseases. A key feature of our application is the inclusion of a Pilot Project Program that will provide start- up funds (up to $5,000 per award) to develop new protocols (or extend existing ones) to enable the LC/MS/MS core laboratory to acquire additional lipid analysis protocols to add to its list of analytical services. We propose to fund 8 Pilot Projects that will drive the acquisition and development of additional analytical protocols. This will bring new users to the core laboratory and enhance the value of the instrument for all users. PUBLIC HEALTH RELEVANCE: Lipids have fundamental roles in both the prevention and the development of all of the major chronic diseases, including cardiovascular disease, diabetes, cancer, liver disease, and neurological disease. The precise mechanisms of action of different lipids in preventing or causing chronic diseases are poorly understood. It is however well established that lipids present at very low levels in cells and tissues have important roles as signaling molecules and that the signals generated by these lipid molecules can play significant roles in chronic disease prevention and/or chronic disease development. The research of the investigators who constitute our User Group is focused on unraveling linkages between lipid metabolism and actions, and how these linkages maintain a balance between chronic disease prevention and chronic disease development. The LC/MS/MS instrument proposed for purchase by the application will facilitate this research.